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2.
BMJ Open Ophthalmol ; 9(1)2024 Jun 17.
Article in English | MEDLINE | ID: mdl-38886120

ABSTRACT

BACKGROUND: Graves' ophthalmopathy is a complex autoimmune disorder that can significantly affect quality of life (QoL), vision and physical appearance. Recently, a deeper understanding of the underlying pathogenesis has led to the development of novel treatment options. AIMS: The purpose of this review is to explore the current literature on conventional and novel treatment modalities and to evaluate which interventions provide the most favourable psychological and clinical outcomes in patients with moderate to severe, active Grave's ophthalmopathy. For example, QoL is an important psychosocial outcome of disease management. However, available literature demonstrates that not all clinically effective treatment options improve patients' QoL. METHODS: A systematic literature review was conducted to assess the clinical and psychosocial outcomes of different therapies for Graves' ophthalmopathy. An extensive database search of Ovid Medline, Ovid Embase and Cochrane Central Register of Controlled Trials was conducted. Studies generated were reviewed and the relevant selected data were retrieved and analysed. RESULTS: Results showed intravenous steroids, rituximab (RTX), tocilizumab and teprotumumab were all significantly effective in improving Clinical Activity Scores. Orbital radiotherapy showed a slight improvement in proptosis and diplopia. All interventions were safe with few serious adverse events being reported across all studies. All treatment modalities demonstrated beneficial improvements in both components of the Graves' Ophthalmopathy-QoL (QoL) questionnaire, apart from orbital radiotherapy which only demonstrated improvements in the visual functioning subscale. Teprotumumab was identified to be the most effective intervention for improving both clinical and psychosocial outcomes. However, further research needs to be conducted to evaluate its side effect profile and cost-effectiveness. Nonetheless, with time it has the potential to be a first-line treatment option in the management of active moderate to severe Graves' ophthalmopathy.


Subject(s)
Graves Ophthalmopathy , Quality of Life , Humans , Graves Ophthalmopathy/therapy , Graves Ophthalmopathy/psychology , Antibodies, Monoclonal, Humanized/therapeutic use , Rituximab/therapeutic use , Immunologic Factors/therapeutic use , Glucocorticoids/therapeutic use
3.
BMJ Case Rep ; 17(6)2024 Jun 26.
Article in English | MEDLINE | ID: mdl-38926127

ABSTRACT

Autoimmune haemolytic anaemia (AIHA), autoimmune destruction of erythrocytes is most commonly secondary to immunomodulated conditions. The association between AIHA and inflammatory bowel disease (IBD) has been poorly investigated. We aim to report a case of AIHA in a patient with ulcerative colitis (UC) treated with vedolizumab.A case of a woman in her 30s with UC that after the initiation of vedolizumab developed severe anaemia. Due to the absence of visible blood losses and a positive Coombs direct test, the diagnosis of AIHA was established. The patient initially initiated prednisolone with no response. Rituximab had to be introduced. After a few days with this therapy, there was a clinical and analytical improvement.AIHA must be taken into account as a possible cause of anaemia in patients with IBD. The differential diagnosis between IBD or drug-related (namely vedolizumab) as the cause of the AIHA is complex and almost impossible to establish.


Subject(s)
Anemia, Hemolytic, Autoimmune , Antibodies, Monoclonal, Humanized , Colitis, Ulcerative , Gastrointestinal Agents , Rituximab , Humans , Colitis, Ulcerative/drug therapy , Colitis, Ulcerative/complications , Antibodies, Monoclonal, Humanized/adverse effects , Antibodies, Monoclonal, Humanized/therapeutic use , Female , Anemia, Hemolytic, Autoimmune/chemically induced , Anemia, Hemolytic, Autoimmune/drug therapy , Anemia, Hemolytic, Autoimmune/diagnosis , Adult , Rituximab/therapeutic use , Rituximab/adverse effects , Gastrointestinal Agents/therapeutic use , Gastrointestinal Agents/adverse effects , Immunologic Factors/therapeutic use , Immunologic Factors/adverse effects , Treatment Outcome
4.
Front Immunol ; 15: 1390997, 2024.
Article in English | MEDLINE | ID: mdl-38919606

ABSTRACT

Background: The incidence of severe infections (SIs) in patients with autoimmune nephropathy after rituximab (RTX) treatment varies significantly. Our study aims to identify high-risk populations, specifically by comparing the differences in the risk of SIs between patients with primary nephropathy and those with nephropathy in the context of systemic autoimmune diseases (referred to as secondary nephropathy). Methods: This retrospective cohort study investigated the occurrence of SIs in adult patients with immune-related kidney disease who received RTX treatment at our institution from 2017 to 2022. Multivariable COX regression models were used to analyze the association between the type of nephropathy (primary or secondary) and SIs. Propensity score analyses, subgroup analyses, and E-value calculations were performed to ensure the reliability of the results. Results: Out of 123 patients, 32 (26%) developed 39 cases of SIs during a mean follow-up period of 19.7 ± 14.6 months post-RTX treatment, resulting in an incidence rate of 18.9/100 patient-years. The multivariable COX regression analysis indicated that patients with secondary nephropathy had a significantly higher risk of SIs compared to those with primary nephropathy (HR = 5.86, 95% CI: 1.05-32.63, P = 0.044), even after accounting for confounding variables including gender, age, BMI, history of prior SIs, baseline eGFR, lymphocyte counts, IgG levels, and the utilization of other immunosuppressive therapies. Various sensitivity analyses consistently supported these findings, with an E-value of 5.99. Furthermore, advanced age (HR: 1.03; 95% CI: 1.01-1.06; P = 0.023), low baseline IgG levels (HR: 0.75; 95% CI: 0.64-0.89; P < 0.001), and recent history of SIs (HR: 5.68; 95% CI: 2.2-14.66; P < 0.001) were identified as independent risk factors. Conclusion: The incidence of SIs following RTX administration in patients with autoimmune nephropathy is significant. It is crucial to note that there are distinct differences between the subgroups of primary and secondary nephropathy. Patients with secondary nephropathy, particularly those who are elderly, have low baseline IgG levels, and have a recent history of SI, are more susceptible to SIs.


Subject(s)
Rituximab , Humans , Rituximab/adverse effects , Rituximab/therapeutic use , Male , Female , Retrospective Studies , Middle Aged , Aged , Adult , Incidence , Infections/etiology , Infections/epidemiology , Autoimmune Diseases/drug therapy , Autoimmune Diseases/epidemiology , Risk Factors , Immunologic Factors/adverse effects , Immunologic Factors/therapeutic use , Kidney Diseases/etiology , Kidney Diseases/epidemiology , Kidney Diseases/chemically induced
5.
Support Care Cancer ; 32(7): 407, 2024 Jun 04.
Article in English | MEDLINE | ID: mdl-38833106

ABSTRACT

OBJECTIVE: Poor adherence to oral chemotherapy adversely impacts clinical outcomes and escalates overall healthcare costs. Despite barriers to medication adherence, a significant gap remains in assessing adherence to oral chemotherapy among multiple myeloma (MM) patients with lower socioeconomic status. Hence, our study aims to evaluate immunomodulator adherence in MM patients at a county hospital, primarily serving underrepresented and indigent individuals with low socioeconomic status across the greater Houston area. METHODS: Inclusion criteria composed of patients diagnosed with MM, aged at least 18 years, and treated with lenalidomide or pomalidomide-two widely used immunomodulators-for a minimum of 2 months or having two or more records of dispensation between May 2019 and May 2021. Adherence was gauged using an adjusted version of the medication possession ratio (MPR). RESULTS: Sixty-two patients were enrolled, yielding a mean MPR value of 88% (SD, ± 18.9). Of these, 43 patients (69.3%) demonstrated adherence with an MPR of ≥ 0.90. A significant difference was found in treatment duration between the adherent (mean 8.8 months; SD, ± 7.2) and non-adherent (mean 13.4 months; SD, ± 7.9) groups (p = 0.027). Notably, race/ethnicity demonstrated a significant difference (p = 0.048), driven by disparities in African American and Hispanic representation across adherence levels. CONCLUSION: In summary, our findings highlight race and treatment duration to be predictors of immunomodulator adherence among MM patients with lower socioeconomic status. Further research is imperative to devise and test innovative interventions aimed at enhancing medication adherence, thereby contributing to improved survival and healthcare quality in this population.


Subject(s)
Lenalidomide , Medication Adherence , Multiple Myeloma , Social Class , Thalidomide , Humans , Multiple Myeloma/drug therapy , Male , Retrospective Studies , Medication Adherence/statistics & numerical data , Female , Middle Aged , Aged , Thalidomide/therapeutic use , Thalidomide/analogs & derivatives , Thalidomide/administration & dosage , Lenalidomide/administration & dosage , Lenalidomide/therapeutic use , Immunologic Factors/therapeutic use , Immunologic Factors/administration & dosage , Immunomodulating Agents/therapeutic use , Immunomodulating Agents/administration & dosage , Immunomodulating Agents/pharmacology , Texas , Aged, 80 and over , Adult
6.
Mult Scler Relat Disord ; 87: 105638, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38713966

ABSTRACT

BACKGROUND: The therapeutic scenario in multiple sclerosis (MS) has evolved over recent years with the progressive introduction of new drugs focused to better balance efficacy, safety and management requirements. The objective of this study was to examine the prescribing patterns of disease-modifying therapies (DMT) over time and across different geographic areas, and the latency between disease onset, first Register center visit, disease diagnosis, and the start of treatment in a large cohort of persons with MS from the Italian Multiple Sclerosis and Related Disorders Register. METHODS: Up to 2022, the Register collected data from 124 centers on more than 78,000 persons, of whom 56,872 received at least one DMT prescription. Beside baseline demographic and clinical characteristics, we focused on DMT according to their efficacy distinguishing between moderate-efficacy (ME), or high-efficacy (HE). RESULTS: There was a higher probability of prescribing HE-DMT for increasing calendar years (multivariable odds ratio, OR=11.51 in 2021 or thereafter vs before 2000), in males (OR=1.08 vs females), patients with primary progressive with or without relapse (OR=3.00 vs clinically isolated syndrome), those with a higher Expanded Disability Status Scale score (OR=3.85 for >4 versus 0-1), and those from larger referral centers (OR=1.89 vs smaller ones). Conversely, higher age at onset was associated to a lower probability of prescribing HE-DMT (OR=0.74 at 40 or more vs <20 years). A trend to shorter times was observed in subsequent calendar years for disease onset, first center visit, diagnosis and first DMT prescription. No trend was detected based on the location of the geographic referral centers. The times between disease onset, first center visit, and diagnosis and the first DMT prescription showed significant decreases according to the year, while differences were less evident for the geographic areas. CONCLUSION: This study highlights some factors influencing the choice of HE-DMT, including aspects of both healthcare and clinical phenotype. The absence of a geographic pattern may indicate some homogeneity in DMT prescriptions across different Italian MS centers.


Subject(s)
Multiple Sclerosis , Registries , Humans , Male , Female , Italy , Adult , Middle Aged , Multiple Sclerosis/drug therapy , Multiple Sclerosis/epidemiology , Practice Patterns, Physicians'/statistics & numerical data , Immunologic Factors/therapeutic use , Immunologic Factors/pharmacology , Drug Prescriptions/statistics & numerical data , Young Adult
7.
ACS Appl Bio Mater ; 7(6): 3865-3876, 2024 Jun 17.
Article in English | MEDLINE | ID: mdl-38780243

ABSTRACT

The study presents a first electrochemical method for the determination of the immunomodulator drug Baricitinib (BARI), crucial in managing COVID-19 patients requiring oxygen support. A unique electrode was developed by modifying graphite carbon nickel nanoparticles (NiNPs) with functionalized multiwalled carbon nanotubes (f.MWCNTs), resulting in nanohybrids tailored for highly sensitive BARI detection. Comparative analysis revealed the superior electrocatalytic performance of the nanohybrid-modified electrode over unmodified counterparts and other modifications, attributed to synergistic interactions between f.MWCNTs and nickel nanoparticles. Under optimized conditions, the sensors exhibited linear detection within a concentration range from 4.00 × 10-8 to 5.56 × 10-5 M, with a remarkably low detection limit of 9.65 × 10-9 M. Notably, the modified electrode displayed minimal interference from common substances and demonstrated high precision in detecting BARI in plasma and medicinal formulations, underscoring its clinical relevance and potential impact on COVID-19 treatment strategies.


Subject(s)
Azetidines , COVID-19 , Electrochemical Techniques , Nanotubes, Carbon , Nickel , Purines , Pyrazoles , SARS-CoV-2 , Sulfonamides , Nanotubes, Carbon/chemistry , Sulfonamides/chemistry , Nickel/chemistry , Pyrazoles/chemistry , Humans , Purines/chemistry , Azetidines/chemistry , SARS-CoV-2/immunology , SARS-CoV-2/isolation & purification , COVID-19 Drug Treatment , Materials Testing , Immunologic Factors/chemistry , Immunologic Factors/therapeutic use , Particle Size , Catalysis , Biocompatible Materials/chemistry , Limit of Detection
8.
J Med Case Rep ; 18(1): 245, 2024 May 13.
Article in English | MEDLINE | ID: mdl-38736000

ABSTRACT

BACKGROUND: Natalizumab is a monoclonal antibody used to treat patients with relapsing-remitting multiple sclerosis. Anemia is a recognized side effect, but it is usually mild and of a short duration when natalizumab is stopped. Here, we describe a case of a young woman with severe and especially long lasting anemia associated with treatment with natalizumab, persisting up to a year after treatment was stopped. CASE PRESENTATION: A 24 year-old Caucasian woman with relapsing-remitting multiple sclerosis developed severe transfusion dependent anemia after 27 infusions with natalizumab, which was her first and only treatment for her multiple sclerosis. Extensive hematologic diagnostics did not reveal any malignant cause or any other plausible non-malignant cause for her anemia. The bone marrow was found to be hypercellular, with a maturation arrest of the erythropoiesis and with grade 1-2 fibrosis. No specific treatment for the anemia was given. The hemoglobin level showed signs of spontaneous increase after nearly one year after natalizumab was discontinued. CONCLUSION: Severe anemia can be caused by treatment with natalizumab. This case adds information to the few other similar reported cases, demonstrating the potential duration of the anemia, as well as detailed description of hematologic findings. The mechanism is most likely due to inhibition of α4 subunit of the α4ß1-integrin, which is present on both lymphocytes and erythroid precursor cells.


Subject(s)
Anemia , Multiple Sclerosis, Relapsing-Remitting , Natalizumab , Humans , Natalizumab/adverse effects , Natalizumab/therapeutic use , Female , Multiple Sclerosis, Relapsing-Remitting/drug therapy , Anemia/chemically induced , Young Adult , Immunologic Factors/adverse effects , Immunologic Factors/therapeutic use
9.
CNS Neurosci Ther ; 30(5): e14761, 2024 05.
Article in English | MEDLINE | ID: mdl-38739094

ABSTRACT

BACKGROUND: This study aims to establish and validate a predictive nomogram for the short-term clinical outcomes of myasthenia gravis (MG) patients treated with low-dose rituximab. METHODS: We retrospectively reviewed 108 patients who received rituximab of 600 mg every 6 months in Huashan Hospital and Tangdu Hospital. Of them, 76 patients from Huashan Hospital were included in the derivation cohort to develop the predictive nomogram, which was externally validated using 32 patients from Tangdu Hospital. The clinical response is defined as a ≥ 3 points decrease in QMG score within 6 months. Both clinical and genetic characteristics were included to screen predictors via multivariate logistic regression. Discrimination and calibration were measured by the area under the receiver operating characteristic curve (AUC-ROC) and Hosmer-Lemeshow test, respectively. RESULTS: Disease duration (OR = 0.987, p = 0.032), positive anti-muscle-specific tyrosine kinase antibodies (OR = 19.8, p = 0.007), and genotypes in FCGR2A rs1801274 (AG: OR = 0.131, p = 0.024;GG:OR = 0.037, p = 0.010) were independently associated with clinical response of post-rituximab patients. The nomogram identified MG patients with clinical response with an AUC-ROC (95% CI) of 0.875 (0.798-0.952) in the derivation cohort and 0.741(0.501-0.982) in the validation cohort. Hosmer-Lemeshow test showed a good calibration (derivation: Chi-square = 3.181, p = 0.923; validation: Chi-square = 8.098, p = 0.424). CONCLUSIONS: The nomogram achieved an optimal prediction of short-term outcomes in patients treated with low-dose rituximab.


Subject(s)
Myasthenia Gravis , Nomograms , Rituximab , Humans , Rituximab/therapeutic use , Rituximab/administration & dosage , Myasthenia Gravis/drug therapy , Myasthenia Gravis/diagnosis , Male , Female , Middle Aged , Adult , Retrospective Studies , Immunologic Factors/administration & dosage , Immunologic Factors/therapeutic use , Treatment Outcome , Aged , Young Adult , Receptors, IgG/genetics
12.
Int J Mol Sci ; 25(10)2024 May 14.
Article in English | MEDLINE | ID: mdl-38791391

ABSTRACT

Ocrelizumab (OCR), an anti-CD20 monoclonal antibody, is approved for treating relapsing remitting (RR) and primary progressive (PP) multiple sclerosis (MS). The standard interval dosing (SID) regimen requires intravenous infusions every six months. Experience of extended dosing due to COVID-19 pandemic-related issues suggests that this strategy may provide comparable efficacy while reducing treatment burden and healthcare costs. This study aimed to evaluate clinical effectiveness, changes in B- and T-cell count, and immunoglobulin dynamics associated with extended interval dosing (EID) of ocrelizumab in a real-world setting. We retrospectively included RRMS or PPMS patients treated with OCR that had already received two OCR cycles and with at least 6 months of follow up after the last infusion. EID was defined as a ≥4 weeks delay compared to SID. Clinical outcomes were occurrence of relapses, MRI activity, 6-months confirmed disability progression (CDP) and their combination (No Evidence of Disease Activity, NEDA-3). We also evaluated changes in CD19+ B cell count, CD4+ and CD8+ T cell count, immunoglobulin titers, and occurrence of hypogammaglobulinemia (hypo-Ig). Frequency tests, multivariate regression models, and survival analysis were applied as appropriate. We analyzed data on 93 subjects (75.3% RRMS) for a total of 389 infusions (272 SID, 117 EID). Clinical and MRI activity, CDP, and NEDA 3 did not significantly differ between EID and SID. EID was associated with lower rates of B-cell depletion. T-cell dynamics and incidence of hypo-Ig were comparable following EID and SID. Hypo-IgG at index infusion was associated with further occurrence of hypo-IgG; male sex and hypo-IgM at index infusion were independently associated with hypo-IgM. In conclusion, OCR EID does not impact MS clinical and radiological outcomes, although it interferes with B-cell dynamics. These findings provide support for a tailored schedule of OCR in MS.


Subject(s)
Antibodies, Monoclonal, Humanized , Humans , Female , Male , Adult , Antibodies, Monoclonal, Humanized/administration & dosage , Antibodies, Monoclonal, Humanized/therapeutic use , Middle Aged , Retrospective Studies , B-Lymphocytes/immunology , B-Lymphocytes/drug effects , Multiple Sclerosis/drug therapy , Multiple Sclerosis/immunology , Treatment Outcome , COVID-19/immunology , Multiple Sclerosis, Relapsing-Remitting/drug therapy , Multiple Sclerosis, Relapsing-Remitting/immunology , SARS-CoV-2/immunology , Immunologic Factors/administration & dosage , Immunologic Factors/therapeutic use
13.
J Clin Neuromuscul Dis ; 25(4): 184-196, 2024 Jun 01.
Article in English | MEDLINE | ID: mdl-38771228

ABSTRACT

OBJECTIVES: To demonstrate treatment efficacy on composite and non-length-dependent (NLD) punch biopsy specimens from intravenous immunoglobulin (IVIG) in pure small-fiber neuropathy (SFN) with trisulfated heparin disaccharide (TS-HDS), fibroblast growth factor-3 (FGFR-3), or Plexin D1 antibodies. SFN has an increasing prevalence, and over 30% of cases may be immune-mediated. TS-HDS, FGFR-3, and Plexin D1 autoantibodies have been shown to be present in 44%-55% of cryptogenic SFN cases, suggesting an immune mechanism. Reports have shown IVIG to be effective for this condition, but some controversy exists based on length-dependent (LD) post-IVIG treatment data in a recent trial. METHODS: In a retrospective review, all pure SFN cases tested for the 3 antibodies from January 2021 to May 2022 were tabulated, and patients who underwent IVIG treatment were separated and analyzed for changes in epidermal nerve fiber density (ENFD) on skin biopsy, as well as SFN-specific questionnaire and pain scores. RESULTS: Ninety-one patients with pure SFN had antibody testing. Sixty of these (66%) were seropositive, and 31 (34%) were seronegative. Seventeen seropositive patients (13 female patients, 4 male patients, 6 FGFR-3, 2 TS-HDS, 4 Plexin D1, 2 with all 3 antibodies, 1 with FGFR-3 and Plexin D1, 1 with FGFR-3 and TS-HDS, and 1 with TS-HDS and Plexin D1) underwent IVIG treatment. Of these, 2 patients stopped treatment due to side effects, and the remaining 15 completed at least 6 months of IVIG. Of these, 12 had a post-IVIG skin biopsy, and of these, 11 (92%) had a 55.1% improved mean composite ENFD (P = 0.01). NLD-ENFD specimens improved by 42.3% (P = 0.02), and LD-ENFD specimens improved by 99.7% (P = 0.01). Composite ENFD in Plexin D1-SFN patients improved by 139% (P = 0.04). In addition, 14 patients had questionnaires pre-IVIG/post-IVIG, and average pain decreased by 2.7 (P = 0.002). CONCLUSIONS: IVIG shows disease-modifying effect in immune SFN with novel antibodies, especially Plexin D1-SFN, as well as significantly improved pain. NLD-ENFD should be examined as well as LD-ENFD to see this effect. Further randomized controlled trials looking at NLD-ENFD as well as LD-ENFD improvement, along with pain and SFN-specific questionnaires, are needed to confirm these findings.


Subject(s)
Autoantibodies , Immunoglobulins, Intravenous , Skin , Small Fiber Neuropathy , Humans , Small Fiber Neuropathy/drug therapy , Female , Male , Middle Aged , Immunoglobulins, Intravenous/therapeutic use , Retrospective Studies , Autoantibodies/blood , Adult , Aged , Biopsy , Skin/pathology , Heparin/therapeutic use , Heparin/analogs & derivatives , Nerve Tissue Proteins/immunology , Treatment Outcome , Receptors, Cell Surface , Immunologic Factors/therapeutic use , Disaccharides
14.
Pediatr Rheumatol Online J ; 22(1): 50, 2024 May 01.
Article in English | MEDLINE | ID: mdl-38693550

ABSTRACT

BACKGROUND: This study investigates the incidence of ocular involvement in Kawasaki disease (KD) and evaluates the relationship between ocular manifestations, laboratory findings, echocardiographic findings, and intravenous immunoglobulin (IVIG) resistance. METHODS: We conducted a cross-sectional study with 58 KD patients from June 2021 to March 2023. For all patients, a complete ophthalmologic examination and echocardiography were performed in the acute phase before starting the treatment. We analyzed the age, sex, mean of white blood cell (WBC) count, platelet count, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST), echocardiographic findings and IVIG responses for all patients and compared the group with ocular involvement with the group without involvement. RESULTS: The incidence of bilateral acute conjunctivitis was 70.7%, while that of acute uveitis was 30%. Patients with uveitis had significantly higher rates of Coronary artery dilatation and IVIG resistance, as well as higher mean levels of WBC, platelet, and CRP compared to those without uveitis. (P < 0.05). Additionally, the age of patients with uveitis involvement was lower than those without involvement. No significant relationships existed between ESR, AST, or ALT values and uveitis (P > 0.05). Furthermore, no significant correlations existed between any examined items and acute bilateral conjunctivitis. CONCLUSION: Uveitis in KD is significantly associated with coronary artery dilatation, IVIG resistance, higher WBC count, platelet count, and CRP level.


Subject(s)
Drug Resistance , Echocardiography , Immunoglobulins, Intravenous , Mucocutaneous Lymph Node Syndrome , Humans , Mucocutaneous Lymph Node Syndrome/epidemiology , Mucocutaneous Lymph Node Syndrome/drug therapy , Mucocutaneous Lymph Node Syndrome/blood , Mucocutaneous Lymph Node Syndrome/physiopathology , Immunoglobulins, Intravenous/therapeutic use , Male , Female , Cross-Sectional Studies , Echocardiography/methods , Child, Preschool , Infant , Child , Uveitis/etiology , Uveitis/epidemiology , Conjunctivitis/etiology , Conjunctivitis/epidemiology , Incidence , C-Reactive Protein/analysis , C-Reactive Protein/metabolism , Blood Sedimentation , Leukocyte Count , Immunologic Factors/therapeutic use , Platelet Count
15.
Medicine (Baltimore) ; 103(19): e38103, 2024 May 10.
Article in English | MEDLINE | ID: mdl-38728448

ABSTRACT

RATIONALE: Thrombotic thrombocytopenic purpura (TTP) is a rare thrombotic microangiopathy caused by reduced activity of the von Willebrand factor-cleaving protease (ADAMTS13), which can be life-threatening. The patient reported in this case study also had concurrent Sjögren syndrome and renal impairment, presenting multiple symptoms and posing a great challenge in treatment. PATIENT CONCERNS: A 25-year-old woman in the postpartum period visited the hospital due to indifference in consciousness for more than 1 day following cesarean section 8 days prior. DIAGNOSIS: Notable decreases were observed in platelets, hemoglobin, creatinine, and ADAMTS13 levels. After a consultative examination by an ophthalmologist, she was diagnosed with retinal hemorrhage in the right eye and dry eye syndrome in both eyes. INTERVENTIONS: Having been diagnosed with TTP with Sjögren syndrome and renal impairment, she received repeated treatments with plasmapheresis combined with rituximab. OUTCOMES: Following treatment and during the follow-up period, the patient's platelet counts and bleeding symptoms significantly improved. LESSONS: TTP has a high mortality rate, and when combined with Sjögren syndrome and renal impairment, it poses an even greater challenge in treatment. However, after administering standard plasmapheresis combined with rituximab treatment, the treatment outcome is favorable.


Subject(s)
Plasmapheresis , Purpura, Thrombotic Thrombocytopenic , Rituximab , Sjogren's Syndrome , Humans , Female , Sjogren's Syndrome/complications , Sjogren's Syndrome/therapy , Plasmapheresis/methods , Adult , Purpura, Thrombotic Thrombocytopenic/therapy , Purpura, Thrombotic Thrombocytopenic/complications , Purpura, Thrombotic Thrombocytopenic/drug therapy , Rituximab/therapeutic use , Rituximab/administration & dosage , Combined Modality Therapy , Renal Insufficiency/therapy , Renal Insufficiency/etiology , Immunologic Factors/therapeutic use , Immunologic Factors/administration & dosage
16.
Expert Opin Pharmacother ; 25(7): 867-884, 2024 May.
Article in English | MEDLINE | ID: mdl-38803314

ABSTRACT

INTRODUCTION: The neuroimmune system has emerged as a novel target for the treatment of substance use disorders (SUDs), with immunomodulation producing encouraging therapeutic benefits in both preclinical and clinical settings. AREAS COVERED: In this review, we describe the mechanism of action and immune response to methamphetamine, opioids, cocaine, and alcohol. We then discuss off-label use of immunomodulators as adjunctive therapeutics in the treatment of neuropsychiatric disorders, demonstrating their potential efficacy in affective and behavioral disorders. We then discuss in detail the mechanism of action and recent findings regarding the use of ibudilast, minocycline, probenecid, dexmedetomidine, pioglitazone, and cannabidiol to treat (SUDs). These immunomodulators are currently being investigated in clinical trials described herein, specifically for their potential to decrease substance use, withdrawal severity, central and peripheral inflammation, comorbid neuropsychiatric disorder symptomology, as well as their ability to improve cognitive outcomes. EXPERT OPINION: We argue that although mixed, findings from recent preclinical and clinical studies underscore the potential benefit of immunomodulation in the treatment of the behavioral, cognitive, and inflammatory processes that underlie compulsive substance use.


Subject(s)
Substance-Related Disorders , Humans , Substance-Related Disorders/drug therapy , Substance-Related Disorders/immunology , Animals , Immunologic Factors/therapeutic use , Immunomodulating Agents/therapeutic use , Immunomodulating Agents/pharmacology , Off-Label Use , Alcoholism/drug therapy , Alcoholism/immunology , Immunomodulation
17.
Skin Therapy Lett ; 29(3): 1-4, 2024 May.
Article in English | MEDLINE | ID: mdl-38781951

ABSTRACT

Intravenous immune globulin (IVIG) is a manufactured blood product commonly used to treat immunodeficiency syndromes, inflammatory disorders, and autoimmune diseases of the skin. The use of IVIG in dermatology has evolved and expanded over time, serving as a useful therapeutic intervention for several inflammatory skin disorders. In addition to demonstrating efficacy in treating several cutaneous pathologies, IVIG also mitigates the need for steroids or other immunosuppressant medications in many dermatologic diseases. This review highlights the evidence for IVIG use across several dermatologic conditions, emphasizing the dosing regimens and safety considerations.


Subject(s)
Immunoglobulins, Intravenous , Skin Diseases , Humans , Immunoglobulins, Intravenous/therapeutic use , Immunoglobulins, Intravenous/administration & dosage , Skin Diseases/drug therapy , Immunologic Factors/therapeutic use , Immunologic Factors/administration & dosage
18.
J Neurol Sci ; 461: 123052, 2024 Jun 15.
Article in English | MEDLINE | ID: mdl-38797140

ABSTRACT

BACKGROUND: Knowledge of the safety and efficacy of disease-modifying therapies (DMTs) in older patients with Multiple Sclerosis (pwMS) is limited due to their exclusion from clinical trials. Our purpose is to evaluate the choice of DMTs in pwMS older than 50 years old in a real-world setting. METHODS: Cross-sectional study of pwMS from the Argentine MS and NMOSD Registry. We included patients under 35 and above 50 years old prescribed DMTs. Disease activity was categorized as highly active (HA) or not highly active (NHA), and DMTs were classified as low efficacy therapies (LET) or high efficacy therapies (HET). RESULTS: 1460 patients (65% females) were enrolled. The HA group comprised 241 patients, 198 young (82.2%) and 43 older (17.8%). The NHA group included 1219 patients, 893 young (73%) and 326 older (27%). In the NHA group, older patients received LET more frequently than younger patients (66% versus 44%; p < 0.01). In the HA group, older patients received LET in 61% of cases, whereas younger patients received HET in 71% (p = 0.01). CONCLUSION: The study shows the preference of LET in older patients regardless of disease activity. However it does not demonstrate a difference in disability in older patients based on low vs high efficacy DMTs used, probably due to the design of the study. Further longitudinal studies are warranted to address this issue.


Subject(s)
Multiple Sclerosis , Registries , Humans , Female , Male , Middle Aged , Cross-Sectional Studies , Multiple Sclerosis/drug therapy , Multiple Sclerosis/epidemiology , Adult , Age Factors , Argentina/epidemiology , Aged , Immunologic Factors/therapeutic use
19.
J Neuroimmunol ; 391: 578368, 2024 Jun 15.
Article in English | MEDLINE | ID: mdl-38761652

ABSTRACT

A demographic shift in multiple sclerosis (MS) is leading to an increased number of elderly people with MS (pwMS) and a rise in late-onset MS (LOMS) cases. This shift adds complexity to the treatment management of these patients, due to enhanced treatment-associated risks and the possible interplay between immunosenescence and disease-modifying therapies (DMTs). In the present paper, we performed a systematic review of the current evidence concerning the relationship between aging and treatment management in elderly pwMS. Our literature search identified 35 original studies relevant to this topic. The gathered evidence consistently indicates a diminished efficacy of DMTs in older pwMS, particularly in preventing disability accrual. Against this background, high-efficacy therapies (HETs) appear to show less benefit over moderate-low-efficacy DMTs in older patients. These data mainly derive from observational retrospective studies or meta-analyses conducted on randomized clinical trials (RCTs). RCTs, however, exclude pwMS older than 55 years, limiting our ability to acquire robust evidence regarding this patient group. Regarding treatment discontinuation in elderly pwMS with stable disease, the available data, which mainly focuses on older injectable DMTs, suggests that their suspension appears to be relatively safe in terms of disease activity. Nevertheless, the first RCT specifically targeting treatment discontinuation recently failed to demonstrate the non-inferiority of treatment discontinuation over continuation, in terms of MRI activity. On the other hand, the evidence on the impact of discontinuation on disease progression is more conflicting and less robust. Furthermore, there is an important lack of studies concerning sequestering DMTs and virtually no data on the discontinuation of anti-CD20 monoclonal antibodies. De-escalation strategy is gaining attention as a de-risking approach alternative to complete treatment discontinuation. It may be defined as the decision to shift from HETs to less potent DMTs in elderly pwMS who have a stable disease. This strategy could reduce treatment-related risks, while minimizing the risk of disease activity and progression potentially associated with treatment discontinuation. This approach, however, remains unexplored due to a lack of studies. Given these findings, the present scenario underlines the urgent need for more comprehensive and robust studies to develop optimized, data-driven treatment strategies for elderly pwMS and LOMS, addressing the unique challenges of MS treatment and aging.


Subject(s)
Multiple Sclerosis , Humans , Multiple Sclerosis/drug therapy , Aged , Aging/immunology , Immunologic Factors/therapeutic use
20.
J Clin Neurosci ; 125: 76-82, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38759351

ABSTRACT

BACKGROUND: Intravenous immunoglobulin (IVIg) and plasmapheresis (PLEX) are recommended in moderate to severe Guillain-Barré Syndrome (GBS), but there is paucity of studies evaluating its effect on nerve conduction studies (NCS). We report the effect of IVIg and PLEX on the NCS parameters and clinical outcomes compared to natural course (NC) of GBS patients. METHOD: Moderate to severe GBS patients were included based on clinical, cerebrospinal fluid, and NCS finding. Six motor and sensory nerves were evaluated at admission, one month and 3 months, and NCS subtyping was done. Axonal and demyelination burden in motor nerves and early reversible conduction block (ERCB) were noted. Patients receiving IVIg, PLEX or on NC were noted. Outcome was defined at 3 months into complete, partial and poor using a 0-6 GBS Disability Scale (GBSDS). RESULT: Seventy-two patients were included, whose median age was 36 years and 22(30.6 %) were females. 44 patients received IVIg, 9 PLEX and 19 were in NC, and they had comparable peak disability. AIDP was the dominant subtype at admission (58.3 %), which remained so at 3 months (50 %). The shift of subtypes was the highest from the equivocal group followed by AMAN and the least from AIDP. IVIg and PLEX group had more reduction in axonal burden and had ERCB compared to NC. 33(44 %) patients had complete recovery, and 40(55.5 %) patients had concordance in clinical and neurophysiological outcome. CONCLUSION: Transition of GBS subtype may occur at follow-up from all the subtypes, the highest from the equivocal and the lowest from the AIDP group. IVIg/PLEX treatment may help in reducing conduction block and axonal burden.


Subject(s)
Guillain-Barre Syndrome , Immunoglobulins, Intravenous , Neural Conduction , Plasmapheresis , Humans , Guillain-Barre Syndrome/therapy , Guillain-Barre Syndrome/physiopathology , Immunoglobulins, Intravenous/therapeutic use , Immunoglobulins, Intravenous/administration & dosage , Female , Male , Adult , Plasmapheresis/methods , Neural Conduction/physiology , Neural Conduction/drug effects , Middle Aged , Young Adult , Treatment Outcome , Immunologic Factors/therapeutic use , Immunologic Factors/administration & dosage , Adolescent
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